How subvisible particles become invisible-relevance of the refractive index for protein particle analysis
How subvisible particles become invisible-relevance of the refractive index for protein particle analysis
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DOI：
10.1002/jps.23479
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发表时间：
2013-05-01
影响因子：
3.8
通讯作者：
Hawe, Andrea
中科院分区：
文献类型：
--
作者：
Zoells, Sarah;Gregoritza, Manuel;Hawe, Andrea
本研究的目的是通过光遮蔽(LO)和微流成像(MFI)技术定量评估透明度和折射率(RI)在蛋白质颗粒分析中的相关性。建立了一种测定蛋白质颗粒相对分子质量的新方法，对来自两种不同蛋白质的蛋白质颗粒测定的相对分子质量指数为1.41。药学上相关水平的高蛋白质浓度和/或糖类增加了配方的RI，导致LO和MFI所确定的亚可见颗粒浓度被严重低估。RI匹配甚至导致粒子对系统不可见，即不再能被LO和MFI检测到。为了确定配方RI对颗粒测量的影响，我们建议使用聚四氟乙烯(PTFE)颗粒来测试RI效应的特定配方。在RI影响的情况下，我们还建议使用与光无关的技术，如共振质量测量(RMM)(阿基米德)，用于蛋白质配方中的亚可见颗粒分析。(C)2013年威利期刊公司和美国药剂师协会药学杂志第102期：14341446期，2013年
The aim of the present study was to quantitatively assess the relevance of transparency and refractive index (RI) on protein particle analysis by the light-based techniques light obscuration (LO) and Micro-Flow Imaging (MFI). A novel method for determining the RI of protein particles was developed and provided an RI of 1.41 for protein particles from two different proteins. An increased RI of the formulation by high protein concentration and/or sugars at pharmaceutically relevant levels was shown to lead to a significant underestimation of the subvisible particle concentration determined by LO and MFI. An RI match even caused particles to become invisible for the system, that is, not detectable anymore by LO and MFI. To determine the influence of formulation RI on particle measurements, we suggest the use of polytetrafluoroethylene (PTFE) particles to test a specific formulation for RI effects. In case of RI influences, we recommend also using a light-independent technique such as resonant mass measurement (RMM) (Archimedes) for subvisible particle analysis in protein formulations. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:14341446, 2013